Abstract

BACKGROUND: It is unclear whether the presence of kidney disease modifies the associations of uric acid with cardiovascular events and death. METHODS: In the limited access, public use Atherosclerosis Risk In Communities (ARIC) database, associations of serum uric acid levels with cardiovascular events and death were analysed using a parametric proportional hazards model and the modification of these associations by the presence of CKD was assessed using a likelihood ratio test. RESULTS: Of the 15 366 ARIC participants included in this analysis, 461 had CKD (eGFR <60 ml/min/1.73 m(2)). In both non-CKD and CKD sub-groups, participants with hyperuricaemia (> or = 7 mg/dl in men and > or = 6 mg/dl in women) compared to those with normal serum uric acid levels had higher waist circumference and fasting serum insulin levels. In the entire cohort, in a multivariate parametric proportional hazards model, each mg/dl increase in serum uric acid was associated with an increased hazard of cardiovascular events (HR 1.09, 95% CI 1.05-1.12) and death. A multiplicative interaction term of serum uric acid and CKD when added to the above models was significant (P < 0.001). The likelihood ratio test of the models with and without the interaction term was also significant (P < 0.001). In the non-CKD population, a multivariate analysis after adjusting for comorbidities and metabolic syndrome showed a significant association between hyperuricaemia and mortality (HR 1.18, 95% CI 1.04-1.33) but not for cardiovascular events (HR 1.07, 95% CI 0.96-1.19). In the CKD population, the association was not significant for both mortality and cardiovascular events. CONCLUSION: We conclude that hyperuricaemia is associated with insulin resistance and mortality in the non-CKD population. The presence of CKD attenuates the associations of uric acid with mortality. Interventional studies are warranted to establish the biological role of hyperuricaemia in mortality in non-CKD and CKD populations.